Petition to Delay Biosimilar Game in U.S. Picks up Steam

By Mari SerebrovWashington Editor

While other countries are building a strong lineup of biosimilars, the U.S. entry into the game could be delayed until 2022  if Abbott Laboratories succeeds in making its case that allowing a biosimilar of a reference drug approved before March 23, 2010, would be an illegal government taking of private property.

Abbott's citizen petition, filed last April, picked up support Wednesday when the Washington Legal Foundation (WLF) weighed in on the drugmaker's behalf, urging the FDA to freeze applications on biosimilars based on biologics approved before Congress gave the agency the authority to develop the regulatory field for the follow-on drugs. (See BioWorld Today, May 7, 2012.)

"Approval of such applications would require use of trade secret information that was submitted to FDA based on assurances that the trade secrets would be maintained," the WLF said, adding that the use of the information "would expose the federal government to massive liability under the Fifth Amendment's Takings Clause."

Prior to the passage of the Biologics Price Competition and Innovation Act (BPCIA) as part of the Affordable Care Act in 2010, makers of innovative biologics had the expectation that trade secrets shared with the FDA would remain secret, Abbott said in its petition. The Abbott Park, Ill.-based company noted that FDA officials had repeatedly assured biologic sponsors that it would neither release the confidential data nor use the information to benefit potential competitors.

Since sponsors of biologics approved before 2010 were told their data would remain secret, Abbott said approving a biosimilar referencing pre-enactment biologic license applications is tantamount to an unconstitutional taking of private property.

Because of the complexity of biologics, they can't be reverse-engineered to create a duplicate as can be done with a small-molecule drug. So, in permitting the biosimilar path, the BPCIA gave the FDA the authority to use the safety and effectiveness data submitted by the sponsor of the reference product in its approval of a biosimilar  but only after the reference biologic has been on the market for 12 years.

All the blockbuster biologics facing U.S. patent expiration in the next few years, including Abbott's Humira (adalimumab), were approved before 2010. According to the newest BioWorld Data report, The Biosimilars Game: A Scorecard for Opportunities, Threats and Critical Strategies, at least nine companies worldwide are developing biosimilars of adalimumab, which hit nearly $8 billion in global sales in 2011 and loses some patent protection in 2016.

For instance, Boehringer Ingelheim GmbH completed a U.S. Phase I pharmacokinetic trial last year for its Humira biosimilar, and Fujifilm Kyowa Kirin Biologics Co. Ltd. plans to begin European trials the first half of this year for its biosimilar, which it hopes to launch by 2018. Recently, Amgen Inc. revealed that it's developing a Humira biosimilar through its partnership with Actavis Inc., formerly Watson Pharmaceuticals Inc. (See BioWorld Today, Feb. 8, 2013.)

Echoing concerns raised in Abbott's petition, Richard Samp, the WLF's chief counsel, said approving biosimilars without giving serious consideration to Fifth Amendment compensation claims "would seriously erode both property rights and public confidence in the reliability of government promises.

"If FDA determines that it is free to ignore its past promises of confidentiality to [biologics] applicants, businesses subject to government regulation will be less willing in the future to spend the massive sums necessary to develop innovative and life-saving products," he warned.

Should Abbott succeed in its petition with the FDA, or in the courts, Humira and other biologics approved prior to 2010 would still face biosimilar competition in other countries. In the U.S., their competition would be limited to new therapies and next-generation products.

But that's not to say they would never see biosimilar competition in the U.S. As the science evolves, the FDA and makers of biosimilars could find a way around the use of confidential data. Or the government could negotiate compensation for its seizure of the trade secrets or exercise eminent domain.

So far, the petition is a bit of a moot point, as the FDA is still waiting for the first biosimilar application to be submitted. As of Jan. 18, the agency had received 50 meeting requests to discuss biosimilar development programs for 12 different reference products, and it had held 37 meetings with sponsors. It also had received 13 investigational new drug applications for biosimilar development programs.

Biosimilars to Hit Egypt

Joining the growing number of nations with distinct regulatory paths for biosimilars, Egypt recently released draft guidelines that would recognize biosimilars approved elsewhere and create a path for biosimilars being developed specifically for the Egyptian market.

Under the guidelines, a biosimilar should reference a biologic licensed in Egypt or licensed and widely marketed in a "reference country" for at least four years. It also should have the same dosage form, strength and route of administration as the reference drug. (Note the use of the word should.)

Sponsors of biosimilars approved outside of Egypt may submit a final dossier, provided their product was developed under the supervision of the regulatory authority in the country where it was manufactured. Egyptian regulators will only evaluate the final product.

Biosimilars manufactured in Egypt will be approved under a step-wise approach that includes a complete chemical, manufacturing and controls development process; comparability quality exercise; and reduced preclinical and clinical head-to-head comparability studies.

Sponsors may change the host cell type for a biosimilar only if they provide data proving that the structure of the biologic is not affected and that the clinical profile will not change. No changes in host cell type will be permitted for glycoproteins  such as darbepoetin alpha (Aranesp, Amgen Inc.), etanercept (Enbrel, Amgen/Pfizer Inc.), epoetin alfa (Epogen/Procrit/Eprex, Amgen/Janssen Pharmaceutica NV) and some interferon products  because glycosylation patterns vary significantly between different host cell types, according to the guidelines.

Sponsors should submit a pharmacovigilance plan along with the marketing authorization application. The plan should include a protocol for a postmarket immunogenicity study. The guidelines don't address exclusivity, but they allow extrapolation for additional indications if certain conditions are met.

Mylan, Biocon Sign Insulin Deal

Building on their 2009 partnership to develop five undisclosed biosimilar monoclonal antibodies, Mylan Inc. and Biocon Ltd. entered an exclusive strategic collaboration to develop and commercialize generic versions of three insulin analogue products.

The deal gives Mylan, of Pittsburgh, the rights to develop and market Biocon's Glargine (a generic of Sanofi SA's Lantus), Lispro (a generic of Eli Lilly and Co.'s Humalog) and Aspart (a generic of Novo Nordisk A/S' NovoLog). Total global net sales of the brand products in 2012 were about $11.5 billion.

Mylan and Biocon will share development, capital and certain other costs, and Mylan will have exclusive commercialization rights in Australia, Canada, Europe, New Zealand and the U.S. through a profit-share arrangement with its Bangalore, India-based partner. The companies will have co-exclusive commercialization rights in certain other markets.